Bladder pain syndromes are common and especially prevalent in women. One of the problems in treating bladder pain is that our fundamental knowledge of nociceptive signaling in the bladder is limited. For example, nociceptive innervation in the bladder and the precise localization of key nociceptive receptors are not well defined. Further, there is considerable controversy as to whether TRPV1, a major pain receptor, is expressed in the bladder urothelium. TRPA1, another important nociceptive channel, has been identified in bladder but not rigorously localized. Non-specific antibody labeling, and the preferential use of male rodents are major limitations of previous studies. The goal of this project is to exploit genetic mouse models to: 1) precisely map nociceptive nerve input to the male and female mouse bladder at different developmental stages, 2) unambiguously localize expression of key nociceptive channels, TRPV1 and TRPA1, to nerves and/or other tissues, and 3) confirm bone fide function of these channels in identified cells/tissu layers. At the conclusion we will be able to submit to GUDMAP the expression of the TRPV1 gene lineage, TRPV1 and TRPA1 in bladder relative to specific tissue anchor genes.